Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma
Language English Country Ireland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26431916
DOI
10.1016/j.lungcan.2015.09.021
PII: S0169-5002(15)30065-9
Knihovny.cz E-resources
- Keywords
- Early diagnosis, Epigenetic biomarkers, Lung cancer, Mesothelin, Mesothelioma, Methylated gene thrombomodulin, miR-126,
- MeSH
- Epigenesis, Genetic * MeSH
- GPI-Linked Proteins blood genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Mesothelioma, Malignant MeSH
- DNA Methylation MeSH
- Mesothelin MeSH
- Mesothelioma blood diagnosis etiology genetics therapy MeSH
- MicroRNAs blood genetics MeSH
- Biomarkers, Tumor * MeSH
- Lung Neoplasms blood diagnosis etiology genetics therapy MeSH
- Prognosis MeSH
- Multidrug Resistance-Associated Proteins blood MeSH
- Reproducibility of Results MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ABCC5 protein, human MeSH Browser
- GPI-Linked Proteins MeSH
- Mesothelin MeSH
- MicroRNAs MeSH
- MIRN126 microRNA, human MeSH Browser
- Biomarkers, Tumor * MeSH
- Multidrug Resistance-Associated Proteins MeSH
OBJECTIVES: Malignant mesothelioma (MM) is a highly aggressive tumor with poor prognosis. A major challenge is the development and application of early and highly reliable diagnostic marker(s). Serum biomarkers, such as 'soluble mesothelin-related proteins' (SMRPs), is the most studied and frequently used in MM. However, the low sensitivity of SMRPs for early MM limits its value; therefore, additional biomarkers are required. In this study, two epigenetically regulated markers in MM (microRNA-126, miR-126, and methylated thrombomodulin promoter, Met-TM) were combined with SMRPs and evaluated as a potential strategy to detect MM at an early stage. MATERIALS AND METHODS: A total of 188 subjects, including 45 MM patients, 99 asbestos-exposed subjects, and 44 healthy controls were prospectively enrolled, serum samples collected, and serum levels of SMRPs, miR-126 and Met-TM evaluated. Logistic regression analysis was performed to evaluate the diagnostic value of the three biomarkers. Using this approach, the performance of the '3-biomarker classifier' was tested by calculating the overall probability score of the MM and control samples, respectively, and the ROC curve was generated. RESULTS AND CONCLUSION: The combination of the three biomarkers was the best predictor to differentiate MM patients from asbestos-exposed subjects and healthy controls. The accuracy and cancer specificity was confirmed in a second validation cohort and lung cancer population. We propose that the combination of the two epigenetic biomarkers with SMRPs as a diagnosis for early MM overcomes the limitations of using SMRPs alone.
Department of Anesthesiology Research Unit IRCCS Orthopaedic Institute Rizzoli Bologna Italy
Department of Clinical and Molecular Sciences Polytechnic University of Marche Ancona Italy
Department of Medical Sciences University of Trieste Trieste Italy
Division of Radiology United Hospitals Ancona Italy
Division of Thoracic Surgery United Hospitals Ancona 60126 Italy
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